In a Multiple Sequence Alignment (MSA) of evolutionary diverse protein sequences, functionally important amino acid residues are observed as conserved sites. It is also known that other less conserved sites influence the native conformation and function of proteins, and are therefore functionally important as well. It is hypothesized that when these sites mutate, this is followed by compensatory mutations elsewhere in the protein so that structure or functionality is preserved. However, such co-evolving sites are not straightforward to identify. [unreadable] [unreadable] This past year we have applied Information theory to the human GPCR proteome to compute non-conserved sites which co-evolve. We have found that for each class of GPCR (i.e. A, B and C), a cohort of amino acid pairs have high mutual information. These amino acids pairs are far part in the sequence and reside in different transmembrane alpha helices. However, using bovine rhodopsin as a guide, we find that these sites are physically close in the folded state possibly indicating that they may be key sites in the ligand binding pocket or for structure.